TENOKSİKAM, PİROKSİKAM VE MELOKSİKAM’IN pKa DEĞERLERİNİN RP-HPLC YÖNTEMİYLE 25℃ VE 37℃’DE THF-SU İKİLİ ORTAMINDA TAYİNİ

Amaç: Bu çalışmada, oksikam grubu ilaç etken maddeleri olan tenoksikam, piroksikam ve meloksikamın hem ağrı ve iltihabı azaltmadaki etkinlikleri hem de farmasötik önemi nedeniyle iyonizasyon sabiti (pKa) değerleri araştırıldı.Gereç ve Yöntem: pKa değerleri, 25 °C ve 37 °C'de tetrahidrofuran-su ikili karışımında (%30-40(h/h)) RP-HPLC yöntemiyle belirlendi. Bu bileşiklerin sudaki pKa değerleri, mol kesri ve Yasuda-Shedlovsky ekstrapolasyon yöntemleri ile değerlendirildi.Sonuç ve Tartışma: Tenoksikam, piroksikam ve meloksikam için 25 °C'de mol kesri yöntemiyle hesaplanan pKa değerleri 5.067 ± 0.037; 5.237 ± 0.065; 4.027 ± 0.144; 37 °C'de pKa değerleri 5.166 ± 0.017; 5.197 ± 0.084; 4.161 ± 0.116. Yasuda-Shedlovsky ekstrapolasyonu ile 25 °C'de hesaplanan pKa değerleri 5.061 ± 0.035; 5.232 ± 0.063; 4.021 ± 0.141; 37 ℃'deki pKa değerleri 5.161 ± 0.013; 5.192 ± 0.053; 4.155 ± 0.094. Sonuçlar, 25 °C'de farklı yöntemler ve farklı çözücüler ile yapılan önceki çalışmalarla uyumludur. Bu çalışma, tetrahidrofuran-su ortamında ve ayrıca vücut fizyolojik sıcaklığı olan 37 °C'de tenoksikam, piroksikam ve meloksikam için yapılan ilk pKa belirleme çalışmasıdır.

Anahtar Kelimeler:

Oksikam, RP-HPLC, THF-su ikili karışımı

DETERMINATION OF pKa VALUES OF TENOXICAM, PIROXICAM AND MELOXICAM BY RP-HPLC AT 25 ℃ AND 37 ℃ IN THF-WATER BINARY MIXTURES

Objective: In this study, the ionization constant (pKa) values of oxicam group drug active ingredients, tenoxicam, piroxicam and meloxicam, were investigated both because of their effectiveness in reducing pain and inflammation and because of their pharmaceutical importance. Material and Method: pKa values were determined by RP-HPLC method in tetrahydrofuran-water binary mixture (30%-40%(v/v)) at 25 °C and 37 °C. The pKa values of these compounds in water were evaluated by mole fraction and Yasuda-Shedlovsky extrapolation methods.Result and Discussion: This study is the first pKa determination study for tenoxicam, piroxicam and meloxicam in tetrahydrofuran-water media and also at 37 ℃, which is body physiological temperature. For tenoxicam, piroxicam and meloxicam, the pKa values calculated by the mole fraction method at 25 °C were 5.067 ± 0.037; 5.237 ± 0.065; 4.027 ± 0.144; pKa values at 37 °C are 5.166 ± 0.017; 5.197 ± 0.084; 4.161 ± 0.116. By Yasuda-Shedlovsky extrapolation, pKa values calculated at 25 ℃ were 5.061 ± 0.035; 5.232 ± 0.063; 4.021 ± 0.141; pKa values at 37 ℃ are 5.161 ± 0.013; 5.192 ± 0.053; 4.155 ± 0.094. The results are in agreement with previous studies with different methods and different solvents at 25 °C.

Keywords:

Oxicam, RP-HPLC, THF-water binary mixtures,

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